JP2000505421A - Cox―2阻害剤のプロドラッグとしてのアルキル化スチレン - Google Patents
Cox―2阻害剤のプロドラッグとしてのアルキル化スチレンInfo
- Publication number
- JP2000505421A JP2000505421A JP9527198A JP52719897A JP2000505421A JP 2000505421 A JP2000505421 A JP 2000505421A JP 9527198 A JP9527198 A JP 9527198A JP 52719897 A JP52719897 A JP 52719897A JP 2000505421 A JP2000505421 A JP 2000505421A
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl
- phenyl
- methyl
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229940111134 coxibs Drugs 0.000 title description 11
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title description 11
- 239000000651 prodrug Substances 0.000 title description 10
- 229940002612 prodrug Drugs 0.000 title description 10
- 125000003011 styrenyl group Chemical class [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 171
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 230000001404 mediated effect Effects 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 (2) diazinyl Chemical group 0.000 claims description 136
- 238000000034 method Methods 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 41
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 229940079593 drug Drugs 0.000 claims description 22
- 125000002950 monocyclic group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 18
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 231100000252 nontoxic Toxicity 0.000 claims description 12
- 230000003000 nontoxic effect Effects 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 9
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 5
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- JFSPBVWPKOEZCB-UHFFFAOYSA-N fenfuram Chemical compound O1C=CC(C(=O)NC=2C=CC=CC=2)=C1C JFSPBVWPKOEZCB-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000005504 styryl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000004306 triazinyl group Chemical group 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 2
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims 3
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 claims 3
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims 3
- 208000027866 inflammatory disease Diseases 0.000 claims 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 abstract description 4
- 102000010907 Cyclooxygenase 2 Human genes 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
- 239000000203 mixture Substances 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- 239000000243 solution Substances 0.000 description 65
- 239000002904 solvent Substances 0.000 description 64
- 238000005481 NMR spectroscopy Methods 0.000 description 52
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
- 239000012267 brine Substances 0.000 description 34
- 239000000460 chlorine Substances 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 28
- 238000003556 assay Methods 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 27
- 241000700159 Rattus Species 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000008280 blood Substances 0.000 description 24
- 210000004369 blood Anatomy 0.000 description 23
- 239000002253 acid Substances 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 239000002585 base Substances 0.000 description 19
- 150000002367 halogens Chemical class 0.000 description 19
- 229910052736 halogen Inorganic materials 0.000 description 18
- 239000003981 vehicle Substances 0.000 description 17
- 229940114079 arachidonic acid Drugs 0.000 description 16
- 235000021342 arachidonic acid Nutrition 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 229920000742 Cotton Polymers 0.000 description 14
- 102000010906 Cyclooxygenase 1 Human genes 0.000 description 14
- 108010037464 Cyclooxygenase 1 Proteins 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 150000002596 lactones Chemical class 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- PIOZZBNFRIZETM-UHFFFAOYSA-L magnesium;2-carbonoperoxoylbenzoic acid;2-oxidooxycarbonylbenzoate Chemical compound [Mg+2].OOC(=O)C1=CC=CC=C1C([O-])=O.OOC(=O)C1=CC=CC=C1C([O-])=O PIOZZBNFRIZETM-UHFFFAOYSA-L 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 7
- 239000012981 Hank's balanced salt solution Substances 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000036765 blood level Effects 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 5
- 239000011651 chromium Substances 0.000 description 5
- 235000008504 concentrate Nutrition 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 150000004820 halides Chemical class 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 229940127293 prostanoid Drugs 0.000 description 5
- 150000003814 prostanoids Chemical class 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 208000005171 Dysmenorrhea Diseases 0.000 description 4
- 206010013935 Dysmenorrhoea Diseases 0.000 description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 239000007859 condensation product Substances 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 210000003608 fece Anatomy 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 201000008482 osteoarthritis Diseases 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 150000003457 sulfones Chemical class 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- BMUDPLZKKRQECS-UHFFFAOYSA-K 3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoic acid iron(3+) hydroxide Chemical compound [OH-].[Fe+3].[N-]1C2=C(C)C(CCC(O)=O)=C1C=C([N-]1)C(CCC(O)=O)=C(C)C1=CC(C(C)=C1C=C)=NC1=CC(C(C)=C1C=C)=NC1=C2 BMUDPLZKKRQECS-UHFFFAOYSA-K 0.000 description 3
- QRVYABWJVXXOTN-UHFFFAOYSA-N 4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1 QRVYABWJVXXOTN-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010065687 Bone loss Diseases 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 229920003091 Methocel™ Polymers 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000001132 Osteoporosis Diseases 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- 208000005107 Premature Birth Diseases 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000005907 cancer growth Effects 0.000 description 3
- MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical class BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 208000010643 digestive system disease Diseases 0.000 description 3
- 125000005594 diketone group Chemical group 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 208000018685 gastrointestinal system disease Diseases 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 229940109738 hematin Drugs 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 3
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 201000008968 osteosarcoma Diseases 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000016160 smooth muscle contraction Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000013222 sprague-dawley male rat Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- HDKLIZDXVUCLHQ-BQYQJAHWSA-N (3E)-3-nonen-2-one Chemical compound CCCCC\C=C\C(C)=O HDKLIZDXVUCLHQ-BQYQJAHWSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DCBXZIWICBQPDL-UHFFFAOYSA-N 2-bromo-1-(4-methylsulfonylphenyl)propan-1-one Chemical compound CC(Br)C(=O)C1=CC=C(S(C)(=O)=O)C=C1 DCBXZIWICBQPDL-UHFFFAOYSA-N 0.000 description 2
- RCHVDUSMVBWVNY-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-(4-methylsulfanylphenyl)propan-1-one Chemical compound CSC1=CC=C(C(=O)C(C)(C)O)C=C1 RCHVDUSMVBWVNY-UHFFFAOYSA-N 0.000 description 2
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 2
- SBPBUYQZVFIIBK-UHFFFAOYSA-N 3-benzoyl-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1C(=O)C1=CC=CC=C1 SBPBUYQZVFIIBK-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- VCJIQNCSXBDKKN-UHFFFAOYSA-N 4-methyl-1,3-thiazole;hydrochloride Chemical compound Cl.CC1=CSC=N1 VCJIQNCSXBDKKN-UHFFFAOYSA-N 0.000 description 2
- OEUFTIBZEDUUCK-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-phenoxyfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC=C1 OEUFTIBZEDUUCK-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 206010006811 Bursitis Diseases 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 208000032170 Congenital Abnormalities Diseases 0.000 description 2
- 208000033131 Congenital factor II deficiency Diseases 0.000 description 2
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 208000012895 Gastric disease Diseases 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000007646 Hypoprothrombinemias Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 201000002481 Myositis Diseases 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- 206010028836 Neck pain Diseases 0.000 description 2
- 239000012425 OXONE® Substances 0.000 description 2
- 206010030124 Oedema peripheral Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 206010038910 Retinitis Diseases 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 208000010040 Sprains and Strains Diseases 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- HUCJFAOMUPXHDK-UHFFFAOYSA-N Xylometazoline Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC1=NCCN1 HUCJFAOMUPXHDK-UHFFFAOYSA-N 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 208000015294 blood coagulation disease Diseases 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- YIYBQIKDCADOSF-ARJAWSKDSA-N cis-pent-2-enoic acid Chemical compound CC\C=C/C(O)=O YIYBQIKDCADOSF-ARJAWSKDSA-N 0.000 description 2
- 230000009852 coagulant defect Effects 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 229940125890 compound Ia Drugs 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 208000007784 diverticulitis Diseases 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000002550 fecal effect Effects 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 208000031169 hemorrhagic disease Diseases 0.000 description 2
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 210000004731 jugular vein Anatomy 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 208000037819 metastatic cancer Diseases 0.000 description 2
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000009240 nasopharyngitis Diseases 0.000 description 2
- 230000010309 neoplastic transformation Effects 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 201000007183 prothrombin deficiency Diseases 0.000 description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 201000003068 rheumatic fever Diseases 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 2
- 229960002218 sodium chlorite Drugs 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 201000004595 synovitis Diseases 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 208000004371 toothache Diseases 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- JTMYHMVWKPSXNE-UHFFFAOYSA-N (1-hydroxycyclopentyl)-(4-methylsulfanylphenyl)methanone Chemical compound C1=CC(SC)=CC=C1C(=O)C1(O)CCCC1 JTMYHMVWKPSXNE-UHFFFAOYSA-N 0.000 description 1
- SODPIMGUZLOIPE-UHFFFAOYSA-N (4-chlorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1 SODPIMGUZLOIPE-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- LHTVMBMETNGEAN-PLNGDYQASA-N (z)-pent-1-en-1-ol Chemical compound CCC\C=C/O LHTVMBMETNGEAN-PLNGDYQASA-N 0.000 description 1
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical compound FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RYSJFJGVYRUSBT-UHFFFAOYSA-N 1-(4-methylsulfonylphenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(S(C)(=O)=O)C=C1 RYSJFJGVYRUSBT-UHFFFAOYSA-N 0.000 description 1
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YSBCNSPSLYEHMZ-UHFFFAOYSA-N 1-phenoxybut-3-en-2-one Chemical compound C=CC(=O)COC1=CC=CC=C1 YSBCNSPSLYEHMZ-UHFFFAOYSA-N 0.000 description 1
- CFJMRBQWBDQYMK-UHFFFAOYSA-N 1-phenyl-1-cyclopentanecarboxylic acid 2-[2-(diethylamino)ethoxy]ethyl ester Chemical compound C=1C=CC=CC=1C1(C(=O)OCCOCCN(CC)CC)CCCC1 CFJMRBQWBDQYMK-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- XGBWXISUZXYULS-UHFFFAOYSA-N 2,3-ditert-butylpyridine Chemical compound CC(C)(C)C1=CC=CN=C1C(C)(C)C XGBWXISUZXYULS-UHFFFAOYSA-N 0.000 description 1
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
- IROWKZOUSZVFER-UHFFFAOYSA-N 2-(3,5-difluorophenyl)ethanethioic s-acid Chemical compound OC(=S)CC1=CC(F)=CC(F)=C1 IROWKZOUSZVFER-UHFFFAOYSA-N 0.000 description 1
- DMYZZZCPJOWSNT-UHFFFAOYSA-N 2-(3-fluorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=CC(F)=C1 DMYZZZCPJOWSNT-UHFFFAOYSA-N 0.000 description 1
- ZBIULCVFFJJYTN-UHFFFAOYSA-N 2-(4-fluorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(F)C=C1 ZBIULCVFFJJYTN-UHFFFAOYSA-N 0.000 description 1
- KEYOKPQFLGLSCR-UHFFFAOYSA-N 2-(4-fluorophenyl)ethanethioic s-acid Chemical compound OC(=S)CC1=CC=C(F)C=C1 KEYOKPQFLGLSCR-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- FOOPZYBJIJNBLQ-UHFFFAOYSA-N 2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanamine Chemical compound NCCOCCOCCOCCOCCOCCN FOOPZYBJIJNBLQ-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 description 1
- XYJYOXRPGNOGEP-UHFFFAOYSA-N 2-bromo-2-methyl-1-(4-methylsulfonylphenyl)propan-1-one Chemical compound CC(C)(Br)C(=O)C1=CC=C(S(C)(=O)=O)C=C1 XYJYOXRPGNOGEP-UHFFFAOYSA-N 0.000 description 1
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- GOLVMRZULJWHGT-UHFFFAOYSA-N 2-cyclohexyloxyacetic acid Chemical compound OC(=O)COC1CCCCC1 GOLVMRZULJWHGT-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- ATPPNMLQNZHDOG-UHFFFAOYSA-N 2-fluoro-2-phenylacetic acid Chemical compound OC(=O)C(F)C1=CC=CC=C1 ATPPNMLQNZHDOG-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- DTCCTIQRPGSLPT-ARJAWSKDSA-N 2-pentenal Chemical compound CC\C=C/C=O DTCCTIQRPGSLPT-ARJAWSKDSA-N 0.000 description 1
- IXOFPUCWZCAFJX-UHFFFAOYSA-N 2-phenylethanethioic s-acid Chemical compound SC(=O)CC1=CC=CC=C1 IXOFPUCWZCAFJX-UHFFFAOYSA-N 0.000 description 1
- MOTOSAGBNXXRRE-UHFFFAOYSA-N 2-phenylsulfanylacetic acid Chemical compound OC(=O)CSC1=CC=CC=C1 MOTOSAGBNXXRRE-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- GADSJKKDLMALGL-UHFFFAOYSA-N 2-propylbenzoic acid Chemical compound CCCC1=CC=CC=C1C(O)=O GADSJKKDLMALGL-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
- GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical compound C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 description 1
- SNYRXHULAWEECU-UHFFFAOYSA-N 3,4-dichlorophenoxyacetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C(Cl)=C1 SNYRXHULAWEECU-UHFFFAOYSA-N 0.000 description 1
- BNPWVUJOPCGHIK-UHFFFAOYSA-N 3,4-difluorophenol Chemical compound OC1=CC=C(F)C(F)=C1 BNPWVUJOPCGHIK-UHFFFAOYSA-N 0.000 description 1
- LFYVNHDFVIPZHV-UHFFFAOYSA-N 3,5-difluorobenzenethiol Chemical compound FC1=CC(F)=CC(S)=C1 LFYVNHDFVIPZHV-UHFFFAOYSA-N 0.000 description 1
- VGLWOZUXEPKTLV-UHFFFAOYSA-N 3-(2,4-difluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C=C1F VGLWOZUXEPKTLV-UHFFFAOYSA-N 0.000 description 1
- MHHIVNMYQIEWDK-UHFFFAOYSA-N 3-(3,4-dichlorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Cl)C(Cl)=C1 MHHIVNMYQIEWDK-UHFFFAOYSA-N 0.000 description 1
- MEVQAQCAEVVVBK-UHFFFAOYSA-N 3-(3,4-difluorophenoxy)-5-methoxy-5-methyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(OC)(C)OC(=O)C=1OC1=CC=C(F)C(F)=C1 MEVQAQCAEVVVBK-UHFFFAOYSA-N 0.000 description 1
- BYTWQLNHRQIQEQ-UHFFFAOYSA-N 3-(4-methylsulfanylphenyl)-2-phenoxycyclopent-2-en-1-one Chemical compound C1=CC(SC)=CC=C1C(CCC1=O)=C1OC1=CC=CC=C1 BYTWQLNHRQIQEQ-UHFFFAOYSA-N 0.000 description 1
- HFLBVHGFPPEJBA-UHFFFAOYSA-N 3-(4-methylsulfonylphenyl)-2-phenoxycyclopent-2-en-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(CCC1=O)=C1OC1=CC=CC=C1 HFLBVHGFPPEJBA-UHFFFAOYSA-N 0.000 description 1
- BWWGQVVECVBFOE-UHFFFAOYSA-N 3-anilino-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1NC1=CC=CC=C1 BWWGQVVECVBFOE-UHFFFAOYSA-N 0.000 description 1
- QBLWJJYEVNVEIT-UHFFFAOYSA-N 3-benzyl-5,5-dimethyl-4-(4-methylsulfanylphenyl)furan-2-one Chemical compound C1=CC(SC)=CC=C1C(C(OC1=O)(C)C)=C1CC1=CC=CC=C1 QBLWJJYEVNVEIT-UHFFFAOYSA-N 0.000 description 1
- KNHHNILXEQGEIW-UHFFFAOYSA-N 3-benzyl-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1CC1=CC=CC=C1 KNHHNILXEQGEIW-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- ARISSSXADTYPHZ-UHFFFAOYSA-N 3-methylsulfonyl-4-phenyl-2h-furan-5-one Chemical compound O=C1OCC(S(=O)(=O)C)=C1C1=CC=CC=C1 ARISSSXADTYPHZ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- KLKVIJCBPREUPJ-UHFFFAOYSA-N 4-(4-methylsulfonylphenyl)-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CCOC1=O KLKVIJCBPREUPJ-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- CEEIJOOHMCRBMH-UHFFFAOYSA-N 4-methylthiophene Chemical compound CC1=[C]SC=C1 CEEIJOOHMCRBMH-UHFFFAOYSA-N 0.000 description 1
- GRDPSSWVXSPXHK-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfanylphenyl)furan-2-one Chemical compound C1=CC(SC)=CC=C1C1=CC(=O)OC1(C)C GRDPSSWVXSPXHK-UHFFFAOYSA-N 0.000 description 1
- SZFUWUOHDRMCKD-UHFFFAOYSA-N 5-chloro-1h-pyridin-2-one Chemical compound OC1=CC=C(Cl)C=N1 SZFUWUOHDRMCKD-UHFFFAOYSA-N 0.000 description 1
- ISKZAFHLGSFFDN-UHFFFAOYSA-N 5-methoxy-5-methyl-4-(4-methylsulfonylphenyl)-3-phenylsulfanylfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(OC)(C)OC(=O)C=1SC1=CC=CC=C1 ISKZAFHLGSFFDN-UHFFFAOYSA-N 0.000 description 1
- JEAVIRYCMBDJIU-UHFFFAOYSA-N 6-methyl-1h-pyridin-2-one Chemical compound CC1=CC=CC(O)=N1 JEAVIRYCMBDJIU-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- XCKHKDIBNRZFGQ-UHFFFAOYSA-N CC(C(=O)C1=CC=C(C=C1)SC)C.BrC(C(=O)C1=CC=C(C=C1)S(=O)(=O)C)(C)C Chemical compound CC(C(=O)C1=CC=C(C=C1)SC)C.BrC(C(=O)C1=CC=C(C=C1)S(=O)(=O)C)(C)C XCKHKDIBNRZFGQ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 102000004961 Furin Human genes 0.000 description 1
- 108090001126 Furin Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 101000605122 Homo sapiens Prostaglandin G/H synthase 1 Proteins 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- QENGPZGAWFQWCZ-UHFFFAOYSA-N Methylthiophene Natural products CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 1
- 241001072332 Monia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000282695 Saimiri Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- MDVUQSWBRKRIBG-UHFFFAOYSA-N [S]CC1=CC=CC=C1 Chemical compound [S]CC1=CC=CC=C1 MDVUQSWBRKRIBG-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000008065 acid anhydrides Chemical group 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- CWNKMHIETKEBCA-UHFFFAOYSA-N alpha-Ethylaminohexanophenone Chemical compound CCCCC(NCC)C(=O)C1=CC=CC=C1 CWNKMHIETKEBCA-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000003040 circulating cell Anatomy 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- WEPUZBYKXNKSDH-UHFFFAOYSA-N cyclopentanecarbonyl chloride Chemical compound ClC(=O)C1CCCC1 WEPUZBYKXNKSDH-UHFFFAOYSA-N 0.000 description 1
- XOVJAYNMQDTIJD-UHFFFAOYSA-N cyclopentobarbital Chemical compound C1CC=CC1C1(CC=C)C(=O)NC(=O)NC1=O XOVJAYNMQDTIJD-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 229960003559 enprostil Drugs 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004991 fluoroalkenyl group Chemical group 0.000 description 1
- 229950004696 flusalan Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- 102000053332 human PTGS1 Human genes 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical class O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- PTOJVMZPWPAXER-VFJVYMGBSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(e,3r)-3-hydroxy-4-phenoxybut-1-enyl]-5-oxocyclopentyl]hepta-4,5-dienoate Chemical compound O[C@@H]1CC(=O)[C@H](CC=C=CCCC(=O)OC)[C@H]1\C=C\[C@@H](O)COC1=CC=CC=C1 PTOJVMZPWPAXER-VFJVYMGBSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960001528 oxymetazoline Drugs 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical class C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 229960003436 pentoxyverine Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229960003893 phenacetin Drugs 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JCRIVQIOJSSCQD-UHFFFAOYSA-N propylhexedrine Chemical compound CNC(C)CC1CCCCC1 JCRIVQIOJSSCQD-UHFFFAOYSA-N 0.000 description 1
- 229960000786 propylhexedrine Drugs 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000000837 restrainer Substances 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical class C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000013389 whole blood assay Methods 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- 229960000833 xylometazoline Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/24—Sulfones; Sulfoxides having sulfone or sulfoxide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/58—One oxygen atom, e.g. butenolide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/64—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/66—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式I [式中、 Xは、 (a) CH2OR6、 (b) C(O)R7、 (c) CH2C(O)CH3、又は (d) CH2CH2COR7 である; R1は、 (a) S(O)2CH3、 (b) S(O)2NH2、 (c) S(O)2NHC(O)CF3、 (d) S(O)(NH)CH3、 (e) S(O)(NH)NH2、及び (f) S(O)(NH)NHC(O)CF3 からなる群から選択される; R2は、 (a) NR8R9、 (b) SR9、 (c) OR9、 (d) R9、 (e) C2-10アルケニル、 (f) C2-10アルキニル、 (g) O、S又はNから選択される1個又は2個のヘテロ原子を含み、場合に よってはカルボニル基又はスルホニル基を含むこともある、一置換、二置換、三 置換又は四置換のヘテロシクロアルキル基(但し置換基は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CN、 (6) CF3、及び (7) C(CH3)2OH からなる群から選択される) (h) スチリル又は置換されたスチリル(但し置換基は、 (1) ハロ、 (2) C1-6アルコキシ、 (3) C1-6アルキルチオ、 (4) CN、 (5) CF3、 (6) C1-10アルキル、 (7) −CO2H、 (8) −C(CH3)2OH、及び (9) ベンジルオキシ からなる群から選択される) (i) フェニルアセチレン又は置換されたフェニルアセチレン(但し置換基は 、 (1) ハロ、 (2) C1-6アルコキシ、 (3) C1-6アルキルチオ、 (4) CN、 (5) CF3、 (6) C1-10アルキル、 (7) −CO2H、 (8) −C(CH3)2OHN及び (9) ベンジルオキシ からなる群から選択される)及び (j) C2-10フルオロアルケニル からなる群から選択される; R3及びR4は各々独立に、C1-10アルキル、CH2OR8、CN、C1-6フルオロ アルキル、非置換又は一置換もしくは二置換のフェニル、非置換又は一置換もし くは二置換のベンジル、非置換又は一置換もしくは二置換のヘテロアリール、非 置換又は一置換もしくは二置換のヘテロアリールメチルである(但し置換基は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CN、及び (6) CF3 からなる群から選択される) あるいは、R3及びR4は、それらが結合する炭素と一緒に、場合によってはO、 S又はNから選択される1個又は2個のヘテロ原子を含んでもよい、3員、4員 、5員、6員又は7員の飽和単環を形成してもよい; R5は、 (a) 水素、 (b) C1-6アルキル、及び (c) C(O)R10 からなる群から選択される; R6は、 (a) 水素、 (b) C1-6アルキル、及び (c) C(O)R10 からなる群から選択される; R7は、 (a) 水素、 (b) OH、 (c) NH2、 (d) OR10、 (e) NHR10、 (f) NR10R11 からなる群から選択される; R8は独立に、 (a) 水素、及び (b) R9 からなる群から選択される; R9は、 (a) C1-10アルキル、 (b) 非置換又は一置換、二置換もしくは三置換のフェニル又はナフチル(但 し置換基は、 (1) ハロ、 (2) C1-10アルコキシ、 (3) C1-10アルキルチオ、 (4) CN、 (5) CF3、 (6) C1-10アルキル、 (7) −CO2H、 (8) べベンジルオキシ からなる群から選択される) (c) 非置換又は一置換、二置換もしくは三置換のヘテロアリール(但しヘテ ロアリールは、5個の原子の単環芳香族環であり、該環はS、O又はNである1 個のヘテロ原子を有し、場合によっては1個、2個又は3個の更なるN原子も有 する;又はヘテロアリールは、6個の原子の単環であり、該環はNである1個の ヘテロ原子を有し、場合によっては1個、2個、3個、又は4個の更なるN原子 を有する、但し置換基は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CN、 (6) CF3 からなる群から選択される) (d) 非置換又は一置換もしくは二置換のベンゾ複素環(但し該複素環は、O 、S又はNから独立に選択される1個又は2個のヘテロ原子を含んでもよく、カ ルボニル基又はスルホニル基を含んでもよい5員、6員又は7員環であり、置換 基は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CN、及び (6) CF3 からなる群から選択される) (e) 非置換又は一置換もしくは二置換のベンゾ炭素環である(但し該炭素環 は、場合によってはカルボニル基を含む5員、6員又は7員環であり、置換基は 、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CN、及び (6) CF3 からなる群から選択される) (f) 一置換又は二置換の、8員、9員又は10員の二環ヘテロアリールであ り、該ヘテロアリールはO、S又はNから独立に選択される2個〜5個のヘテロ 原子を含み、各環内に少なくとも1個のヘテロ原子を含む(但し置換基は、 (1) 水素、 (2) ハロ、 (3) C1-10アルキル、 (4) C1-10アルコキシ、 (5) C1-10アルキルチオ、 (6) CN、及び (7) CF3 からなる群から選択される) からなる群から選択される; R10及びR11は独立に、 (a) C1-10アルキル、 (b) C1-10アルキル−CO2R12、 (c) C1-10アルキル−NR12R13、 (d) (CH2CH2O)nR12(式中、n=1〜200)、 (e) (CH2CH2O)nCH2CH2NR12R13(式中、n=1〜200) からなる群から選択される、 あるいはR10及びR11は、それらが結合する窒素と一緒に、場合によってはO、 S又はN−R12から選択される更なる1個又は2個のヘテロ原子を含んでもよい 、3員、4員、5員、6員又は7員の単環を形成してもよい; R12及びR13は独立に、 (a) 水素、及び (b) C1-10アルキル からなる群から選択される] を有する化合物又は医薬として許容できるその塩。 2. Xは、 (a) CH2OR6、又は (b) C(O)R7 であることを特徴とする請求項1に記載の化合物。 3. Xは、 (a) CH2OR6、 (b) C(O)R7 である; R1は、 (a) S(O)2CH3、 (b) S(O)2NH2、 (c) S(O)2NHC(O)CF3、 からなる群から選択される; R2は、非置換又は一置換、二置換もしくは三置換のフェニル又はナフチルであ る(但し置換基は、 (1) ハロ、 (2) C1-3アルコキシ、 (3) CF3、及び (4) C1-3アルキル からなる群から選択される); R3及びR4は独立に、C1-3アルキル又はC1-3フルオロアルキルである、 あるいは、R3及びR4は、それらが結合する炭素と一緒に、場合によってはO又 はSから選択される1個のヘテロ原子を含んでもよい、3員、4員、5員、又は 6員の単環を形成しても よい; R5は、 (a) 水素、 (b) C1-3アルキル、 (c) C(O)R10 からなる群から選択される; R6は、 (a) 水素、 (b) C1-3アルキル、 (c) C(O)R10 からなる群から選択される; R7は、 (b) OH、 (c) NH2、 (d) OR10、 (e) NHR10、 (f) NR10R11 からなる群から選択される: R10及びR11は独立に、 (a) C1-3アルキル、 (b) C1-6アルキル−CO2R12、 (c) C1-6アルキル−NR12R13、 (d) (CH2CH2O)nR12(式中、n=1〜200)、 (e) (CH2CH2O)nCH2CH2NR12R13(式中、n=1〜200) からなる群から選択される、 あるいはR10及びR11は、それらが結合する窒素と一緒に、場合によってはO、 S又はN−R12から選択される更なる1個のヘテロ原子を含んでもよい、3員、 4員、5員、6員又は7員の単環を形成してもよい; R12及びR13は独立に、 (a) 水素、及び (b) C1-10アルキル からなる群から選択される; ことを特徴とする請求項2に記載の化合物。 4. Xは、 (a) CH2OR6、 (b) C(O)R7 である; R1は、 (a) S(O)2CH3、 (b) S(O)2NH2 からなる群から選択される; R2は、非置換又は一置換、二置換もしくは三置換のフェニル又はナフチルであ る(但し置換基は、 (1) ハロ、 (2) C1-3アルコキシ、 (3) CF3、及び (4) C1-3アルキル からなる群から選択される); R3及びR4は独立に、C1-3アルキル又はC1-3フルオロアルキルである; R5は、 (a) 水素、 (b) メチル、 (c) メトキシ からなる群から選択される; R6は、 (a) 水素、 (b) C1-3アルキル、 (c) C(O)R10 からなる群から選択される; R7は、 (b) OH、 (c) NH2、 (d) OR10、 (e) NHR10、 (f) NR10R11 からなる群から選択される; R10及びR11は独立に、 (a) C1-3アルキル、 (b) C1-6アルキル−CO2R12、 (c) C1-6アルキル−NR12R13、 (d) (CH2CH2O)nR12(式中、n=1、2、3、4又は5)、 (e) (CH2CH2O)nCH2CH2NR12R13(式中、 n=1、2、3、4又は5) からなる群から選択される; R12及びR13は独立に、 (a) 水素、及び (b) C1-4アルキル からなる群から選択される; ことを特徴とする請求項3に記載の化合物。 5. R2はR9であることを特徴とする請求項1に記載の化合物。 6. R9は非置換又は一置換、二置換もしくは三置換のフェニルである(但し 置換基は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CN、 (6) CF3、 (7) −COOH、及び (8) ベンジルオキシ からなる群から選択される); ことを特徴とする請求項5に記載の化合物。 7. R1は、 (a) S(O)2CH3、及び (b) S(O)2NH2 からなる群から選択される; R3及びR4は両方ともC1-3アルキルである; R9は非置換又は一置換、二置換もしくは三置換のフェニルである(但し置換基 は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) −COOH、及び (6) ベンジルオキシ からなる群から選択される); ことを特徴とする請求項6に記載の化合物。 8. Xは、 (a) CH2OR6、 (b) C(O)R7 である; R1は、 (a) S(O)2CH3、 (b) S(O)2NH2、 (c) S(O)2NHC(O)CF3、 からなる群から選択される; R2は、非置換又は一置換、二置換もしくは三置換のヘテロアリールである、但 しヘテロアリールは、5個の原子の単環芳香族環であり、該環はS、O又はNで ある1個のヘテロ原子を有し、場合によっては1個、2個又は3個の更なるN原 子も有する;又はヘテロアリールは、6個の原子の単環であり、該環はNである 1個のヘテロ原子を有し、場合によっては1個、2個、3個、又は4個の更なる N原子を有する(但し置換基は、 (1) ハロ、 (2) C1-10アルキル、 (3) C1-10アルコキシ、 (4) C1-10アルキルチオ、 (5) CF3 からなる群から選択される); R3及びR4は独立に、C1-3アルキル又はC1-3フルオロアルキルである、 あるいは、R3及びR4は、それらが結合する炭素と一緒に、場合によってはO又 はSから選択される1個のヘテロ原子を含んでもよい、3員、4員、5員、又は 6員の単環を形成してもよい; R5は、 (a) 水素、 (b) C1-3アルキル、 (c) C(O)R10 からなる群から選択される; R6は、 (a) 水素、 (b) C1-3アルキル、 (c) C(O)R10 からなる群から選択される; R7は、 (b) OH、 (c) NH2、 (d) OR10、 (e) NHR10、 (f) NR10R11 からなる群から選択される; R10及びR11は独立に、 (a) C1-3アルキル、 (b) C1-6アルキル−CO2R12、 (c) C1-6アルキル−NR12R13、 (d) (CH2CH2O)nR12(式中、n=1〜200)、 (e) (CH2CH2O)nCH2CH2NR12R13(式中、n=1〜200) からなる群から選択される、 あるいはR10及びR11は、それらが結合する窒素と一緒に、場合によってはO、 S又はN−R12から選択される更なる1ヘテロ原子を含んでもよい、3員、4員 、5員、6員又は7員の単環を形成してもよい; R12及びR13は独立に、 (a) 水素、及び (b) C1-10アルキル からなる群から選択される; ことを特徴とする請求項2に記載の化合物。 9. Xは、 (a) CH2OR6、 (b) C(O)R7 である; R1は、 (a) S(O)2CH3、 (b) S(O)2NH2 からなる群から選択される; R2は非置換又は一置換、二置換もしくは三置換のヘテロアリールである(但し アリールは、 (1) フラニル、 (2) ジアジニル、 (3) イミダゾリル、 (4) イソオキサゾリル、 (5) イソチアゾリル、 (6) オキサジアゾリル、 (7) オキサゾリル、 (8) ピラゾリル、 (9) ピリジル、 (10) ピロリル、 (11) テラジニル、 (12) テラゾリル、 (13) チアジアゾリル、 (14) チアゾリル、 (15) チエニル、 (16) トリアジニル、及び (17) トリアゾリル からなる群から選択され、置換基は、 (1) ハロ、 (2) C1-3アルコキシ、 (3) CF3、及び (4) C1-3アルキル からなる群から選択される); R3及びR4は独立にC1-3アルキル又はC1-3フルオロアルキルである; R5は、 (a) 水素、 (b) メチル、 (c) メトキシ からなる群から選択される; R6は、 (a) 水素、 (b) C1-3アルキル、及び (c) C(O)R10 からなる群から選択される; R7は、 (b) OH、 (c) NH2、 (d) OR10、 (e) NHR10、 (f) NR10R11 からなる群から選択される; R10及びR11は独立に、 (a) C1-3アルキル、 (b) C1-6アルキル−CO2R12、 (c) C1-6アルキル−NR12R13、 (d) (CH2CH2O)nR12(式中、n=1、2、3、4又は5)、 (e) (CH2CH2O)nCH2CH2NR12R13からなる群から選択される; R12及びR13は独立に、 (a) 水素、及び (b) C1-4アルキル からなる群から選択される; ことを特徴とする請求項3に記載の化合物。 10. R1はS(O)2CH3であることを特徴とする請求項1に記載の化合物 。 11. R2は非置換又は一置換、二置換もしくは三置換のヘテロアリールであ る(但しアリールは、 (1) フラニル、 (2) ジアジニル、 (3) オキサゾリル、 (4) ピラゾリル、 (5) ピリジル、 (6) ピロリル、 (7) テトラジニル、 (8) テトラゾリル、 (9) チアゾリル、 (10) チエニル、 からなる群から選択され、置換基は、 (1) ハロ、 (2) C1-3アルコキシ、 (3) CF3、及び (4) C1-3アルキル からなる群から選択される; ことを特徴とする請求項9に記載の化合物。 12. R3及びR4は独立に、 (a) メチル、 (b) エチル からなる群から選択される; ことを特徴とする請求項1に記載の化合物。 13. からなる群から選択されることを特徴とする請求項1に記載の化合物又は医薬と して許容できるその塩。 14. (1) 2−(3−フルオロフェニル)−4−メチル−3−(4−(メ チルスルホニル)フェニル)−2−(Z)−ペンテン−1,4−ジオール、 (2) 酢酸4−アセトキシ−2−(3−フルオロフェニル)−4−メチル− 3−(4−メチルスルホニル)フェニル)−2−(Z)−ペント−2−エニルエ ステル、 (3) 2−(3−フルオロフェニル)−4−メトキシ−4−メチル−3−( (4−メチルスルホニル)フェニル)−2−(Z)−ペンテン酸、 (4) N,N−ジメチル−2−(3−フルオロフェニル)−4−メトキシ− 4−メチル−3−(4−メチルスルホニル)フェニル)−2−(Z)−ペンテン アミド、 (5) N−(2−(ジメチルアミノ)エチル)−N−メチル−2−(3−フ ルオロフェニル)−4−メトキシ−4−メチル−3−(4−メチルスルホニル) フェニル)−2−(Z)−ペンテンアミド、 (6) 2−(3−フルオロフェニル)−4−メトキシ−4−メチル−3−( 4−メチルスルホニル)フェニル)−2−(Z)−ペンテン酸メチル、 (7) 2−(3−フルオロフェニル)−4−メトキシ−4−メチル−3−( 4−(メチルスルホニル)フェニル)−2−(Z)−ペンテンアミド、及び (8) N−(2−(2−(2−(2−(2−(2−アミノエトキシ)−エト キシ)−エトキシ)−エトキシ)−エトキシ)−エトキシ)−エチル)−2−( 3−フルオロフェニル)−4−メトキシ−4−メチル−3−(4−(メチルスル ホニル)フェニル)−2−(Z)−ペンテンアミド からなる群から選択されることを特徴とする請求項1に記載の化合物又は医薬と して許容できるその塩。 15. 非ステロイド性抗炎症剤による治療が可能な炎症性疾患の治療用医薬製 剤であって、非毒性量で治療有効量の請求項1〜14のいずれかに記載の化合物 と医薬として許容できる担体を含むことを特徴とする該医薬製剤。 16. COX−1よりもCOX−2を選択的に阻害する活性薬剤で有利に治療 されるシクロオキシゲナーゼ媒介疾患の治療用医薬製剤であって、非毒性量で治 療有効量の請求項1〜14のいずれかに記載の化合物と医薬として許容できる担 体を含むことを特徴とする該医薬製剤。 17. 非ステロイド性抗炎症剤によって治療可能な炎症性疾患の治療方法であ って、このような治療の必要のある患者に、非毒性量で治療有効量の請求項1に 記載の化合物及び医薬として許容できる担体を投与することを特徴とする該方法 。 18. COX−1よりも選択的にCOX−2を阻害する活性薬剤によって有利 に治療されるシクロオキシゲナーゼ媒介疾患の治療方法であって、このような治 療の必要のある患者に、非毒性量で治療有効量の請求項1に記載の化合物を投与 することを特徴とする該方法。 19. 請求項1、2、3、4、5、6、7、8、9、10、11、12、13 又は14に記載の許容可能で抗炎症量の式(I)の化合物又は医薬として許容で きるその塩、並びに医薬として許容できる担体を一緒に含むことを特徴とする抗 炎症医薬製剤。 20. COX−1よりもCOX−2を選択的に阻害する薬剤によって有利に治 療されるシクロオキシゲナーゼ媒介疾患の治療における使用のための請求項1、 2、3、4、5、6、7、8、9、10、11、12、13又は14に記載の式 (I)の化合物又は医薬として許容できるその塩。 21. 非ステロイド性抗炎症剤によって治療可能な炎症性疾患の治療のための 医薬の製造における請求項1、2、3、4、5、6、7、8、9、10、11、 12、13又は14に記載の式(I)の化合物又は医薬として許容できるその塩 の使用。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1043296P | 1996-02-01 | 1996-02-01 | |
GB60/010,432 | 1996-03-18 | ||
GBGB9605646.0A GB9605646D0 (en) | 1996-03-18 | 1996-03-18 | Alkylated styrenes as prodrugs to cox-2 inhibitors |
GB9605646.0 | 1996-03-18 | ||
PCT/CA1997/000058 WO1997028121A1 (en) | 1996-02-01 | 1997-01-29 | Alkylated styrenes as prodrugs to cox-2 inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2000505421A true JP2000505421A (ja) | 2000-05-09 |
JP4004541B2 JP4004541B2 (ja) | 2007-11-07 |
Family
ID=26308948
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP52719897A Expired - Fee Related JP4004541B2 (ja) | 1996-02-01 | 1997-01-29 | Cox―2阻害剤のプロドラッグとしてのアルキル化スチレン |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0882016B1 (ja) |
JP (1) | JP4004541B2 (ja) |
AT (1) | ATE193526T1 (ja) |
AU (1) | AU710675B2 (ja) |
DE (1) | DE69702182T2 (ja) |
ES (1) | ES2147973T3 (ja) |
WO (1) | WO1997028121A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7285435B2 (en) | 2000-12-29 | 2007-10-23 | Lg.Philips Lcd Co., Ltd. | Active matrix organic electroluminescence display device and method for manufacturing the same |
JP2008520569A (ja) * | 2004-11-16 | 2008-06-19 | メルク エンド カムパニー インコーポレーテッド | 卒中を治療するための(2r)−2−プロピルオクタン酸のプロドラッグ |
WO2018138913A1 (ja) * | 2017-01-30 | 2018-08-02 | 株式会社テクノスルガ・ラボ | 保存溶液およびその保存溶液を用いた検体の保存方法、特に、検体のdnaおよび有機酸やポリアミン類などの化学物質の保存溶液およびその保存溶液を用いた保存方法 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE244232T1 (de) * | 1997-03-14 | 2003-07-15 | Merck Frosst Canada Inc | (methylsulfonyl)phenyl-2-(5h)-furanone mit sauerstoff-bindung als cox-2-hemmer |
US6071954A (en) * | 1997-03-14 | 2000-06-06 | Merk Frosst Canada, Inc. | (methylsulfonyl)phenyl-2-(5H)-furanones with oxygen link as COX-2 inhibitors |
ES2326849T3 (es) * | 1999-10-08 | 2009-10-20 | Merial | sin titulo. |
AP2002002582A0 (en) | 1999-12-23 | 2002-09-30 | Nitromed Inc | Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use |
AR038957A1 (es) | 2001-08-15 | 2005-02-02 | Pharmacia Corp | Terapia de combinacion para el tratamiento del cancer |
EP1539679A4 (en) * | 2002-06-28 | 2007-07-04 | Nitromed Inc | OXIM- AND / OR HYDRAZO-CONTAINING, NITROSED AND / OR NITROSYLATED CYCLOOXIGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND USE METHODS |
EP1542972A4 (en) | 2002-07-29 | 2008-01-23 | Nitromed Inc | CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITION AND METHOD OF USE |
DE102004027912A1 (de) * | 2004-06-09 | 2005-12-29 | Grünenthal GmbH | Substituierte Cyclopenten-Verbindungen |
USD889219S1 (en) | 2017-08-04 | 2020-07-07 | Husqvarna Ab | Air outlet for a trimmer |
CA3209491A1 (en) | 2021-03-15 | 2022-09-22 | Saul Yedgar | Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory disease |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU625123B2 (en) * | 1989-04-24 | 1992-07-02 | Otsuka Pharmaceutical Factory, Inc. | 3-halogeno-2,3-diphenylacrylaldehyde derivative, method of production thereof and curing agent for hyperlipidemia |
US5474995A (en) * | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
US5393790A (en) * | 1994-02-10 | 1995-02-28 | G.D. Searle & Co. | Substituted spiro compounds for the treatment of inflammation |
-
1997
- 1997-01-29 AU AU14342/97A patent/AU710675B2/en not_active Ceased
- 1997-01-29 AT AT97900910T patent/ATE193526T1/de not_active IP Right Cessation
- 1997-01-29 DE DE69702182T patent/DE69702182T2/de not_active Expired - Fee Related
- 1997-01-29 JP JP52719897A patent/JP4004541B2/ja not_active Expired - Fee Related
- 1997-01-29 ES ES97900910T patent/ES2147973T3/es not_active Expired - Lifetime
- 1997-01-29 WO PCT/CA1997/000058 patent/WO1997028121A1/en active IP Right Grant
- 1997-01-29 EP EP97900910A patent/EP0882016B1/en not_active Expired - Lifetime
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7285435B2 (en) | 2000-12-29 | 2007-10-23 | Lg.Philips Lcd Co., Ltd. | Active matrix organic electroluminescence display device and method for manufacturing the same |
JP2008520569A (ja) * | 2004-11-16 | 2008-06-19 | メルク エンド カムパニー インコーポレーテッド | 卒中を治療するための(2r)−2−プロピルオクタン酸のプロドラッグ |
WO2018138913A1 (ja) * | 2017-01-30 | 2018-08-02 | 株式会社テクノスルガ・ラボ | 保存溶液およびその保存溶液を用いた検体の保存方法、特に、検体のdnaおよび有機酸やポリアミン類などの化学物質の保存溶液およびその保存溶液を用いた保存方法 |
Also Published As
Publication number | Publication date |
---|---|
EP0882016B1 (en) | 2000-05-31 |
EP0882016A1 (en) | 1998-12-09 |
AU710675B2 (en) | 1999-09-30 |
WO1997028121A1 (en) | 1997-08-07 |
DE69702182T2 (de) | 2001-03-01 |
ATE193526T1 (de) | 2000-06-15 |
JP4004541B2 (ja) | 2007-11-07 |
ES2147973T3 (es) | 2000-10-01 |
DE69702182D1 (de) | 2000-07-06 |
AU1434297A (en) | 1997-08-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5925631A (en) | Alkylated styrenes as prodrugs to COX-2 inhibitors | |
JP4068802B2 (ja) | Cox−2インヒビターとしての(メチルスルホニル)フェニル−2−(5h)−フラノン類 | |
US5733909A (en) | Diphenyl stilbenes as prodrugs to COX-2 inhibitors | |
US6169188B1 (en) | (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors | |
EP0778834B1 (en) | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 | |
JP2788677B2 (ja) | Cox−2阻害剤としてのフェニル複素環 | |
DE69529690T2 (de) | Diaryl-2(5h)-fuaranone als cox-2-inhibitoren | |
US5677318A (en) | Diphenyl-1,2-3-thiadiazoles as anti-inflammatory agents | |
US5981576A (en) | (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors | |
US6057319A (en) | 3,4-Diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to cox-2 inhibitors | |
EP0904269B1 (en) | 3,4-diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to cox-2 inhibitors | |
US5817700A (en) | Bisaryl cyclobutenes derivatives as cyclooxygenase inhibitors | |
US6222048B1 (en) | Diaryl-2-(5H)-furanones as Cox-2 inhibitors | |
JP2000505421A (ja) | Cox―2阻害剤のプロドラッグとしてのアルキル化スチレン | |
CA2244134C (en) | Diphenyl stilbenes as prodrugs to cox-2 inhibitors | |
EP0889878B1 (en) | Bisarylcyclobutene derivates as cyclooxygenase inhibitors | |
JP2004505943A (ja) | シクロオキシゲナーゼ−2阻害薬としてのピロン類 | |
CA2283100A1 (en) | (methylsulfonyl)phenyl-2-(5h)-furanones with oxygen link as cox-2 inhibitors | |
AU711902C (en) | 3,4-diaryl-2-hydroxy-2,5-dihydrofurans as prodrugs to cox-2 inhibitors | |
MXPA98006213A (en) | Diphenylesthylenes as profarmacos for inhibitors of cyclooxygenes |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20060324 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20060324 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20061212 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070309 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20070423 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070611 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20070731 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20070822 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100831 Year of fee payment: 3 |
|
LAPS | Cancellation because of no payment of annual fees |